Modular fluid sample preparation assembly

ABSTRACT

An apparatus for collecting biological fluids and handling the same into a sample for testing comprising a tubular container having open ends, one of which is removably secured to a collection storage unit. A shuttle assembly constructed of a cylindrical hollow piston defining a chamber, a top cover covering one end of said piston and a second cover with an aperture and a connector covering the second end of the piston is slidably mounted in the tubular container. An &#34;O&#34; ring is mounted on the exterior surface of the piston to form a fluid tight seal between the &#34;O&#34; ring and the interior surface of the tubular container with the connector being removably secured to a resin/sample container so that movement of the piston in the tubular container carries the resin/sample container into the collection storage unit and forces fluid collected in the tubular container to flow through the resin/sample container.

This is a division, of application Ser. No. 07/308,763 filed Jan. 10,1989, pending.

BACKGROUND OF THE INVENTION

The present invention is directed to medical and laboratory specimencollecting and testing equipment, and more specifically to an apparatusfor collecting biological fluids for use in testing.

It is generally necessary in diagnosing and testing for many diseases tocollect biological fluids from a patient, e.g., sputum, blood, pleuraland peritoneal cavity fluids, urine, etc. for analysis. It is importantduring the collection handling of biological fluid specimens that thepotential of specimen contamination and the spread of any infection fromthe specimen be minimized. In addition there is also the potential forspecimen damage during the collection and/or shipment process as well asthe potential for destruction of certain components of the specimenbecause the packaging does not screen particulants in the fluids orcollects and holds different fluid components which will negate the testresults or result in false data being obtained when the specimen istested.

It has been noted that one of the problems in collecting biologicalfluid specimens occurs not only during the collection of the specimensbut also in the transport or shipment of the specimens after collectionto the laboratory for analysis.

A typical specimen collecting apparatus is shown by U.S. Pat. 4,741,346.This apparatus includes a base stand which supports the specimen vial inan upright position. A funnel is inserted in the open end of thespecimen vial and surrounds and encloses the upper portion of the vial.The base stand has an upwardly extending tubular wall which at leastpartially surrounds the vial which in connection with the cap and allowsthe user to remove the vial without touching the surface or coming incontact with the specimen. Examples of various types of liquidcontainers for collecting and transporting urine are shown by U.S. Pat.Nos. 3,777,739; 3,881,465; 4,042,337; 4,084,937; 4,244,920; 4,492,258and 4,700,714.

One such specimen collection device shown by U.S. Pat. 4,040,791discloses a collection receptacle having a nipple upon which is mounteda specimen container which receives a predetermined amount of thespecimen in a sealed condition. The specimen container is provided withan integrally formed cap which is placed over the opening in which thecollector nipple is inserted. U.S. Pat. No. 4,557,274 discloses amidstream urine collector having a funnel which transmits urine into acup member which is covered by a membrane cover.

A combined strip testing device and collection apparatus is shown byU.S. Pat. No. 4,473,530 which is directed to an apparatus whichintegrates testing and collection by having chemical reagent test stripspresent within the tube together with specific gravity reading meansallowing immediate testing of the urine. U.S. Pat. No. 4,573,983 isdirected towards a liquid collection system having an antiseptic memberon the discharge section which uses a filter of air and bacteriaimpervious material to filter the urine.

It is therefore desirable to provide an easy to handle apparatus whichobtains fluid samples such as urine with a minimum chance for spillagebetween collection and laboratory as well as a need to separate variouscomponents of the urine. In addition particulates contained in the urinehave a valuable medical use so that concentrating the same isbeneficial. In using the present invention testing can be performedquickly and accurately with minimum time.

For some testing, particularly where antigens are being removed from thebody fluids for a variety of tests it is desirable to remove theantigens from the urine fluid and to concentrate the particulants (e.g.cells, cell debris, etc.) so that various test procedures can be run. Itis also desirable to do so with minimal exposure of laboratory personnelto the sample subject of testing. Previously this has been accomplishedby a series of tests involving a number of different containers andexpensive laboratory equipment. Mass testing using such a series oftests is expensive, time consuming, and often unsatisfactory.

BRIEF SUMMARY OF THE INVENTION

There is provided in the practice of the invention according to thepresently preferred embodiment, a urine and blood collection, processing(filtration, concentration, and partial purification of antigen(s)subject to testing) and analysis device. This device is in the form ofmodular components having a transportable sample compartment in thehousing, which through the use of modules can be washed or treated withother fluids allowing the sample then to be quickly analyzed or placedat a controlled temperature for further experimentation as soon as it isreceived in the laboratory or clinic.

In the accompanying drawings, there is shown an illustrative embodimentof the invention from which these and other of objectives, novelfeatures and advantages will be readily apparent.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross sectional view of separated units of the samplecollection apparatus of the invention;

FIG. 2 is a cross sectional view of an alternate shuttle storage unit ofthe sample collection apparatus of FIG. 1;

FIG. 3 is a cross sectional view of a cap for the shuttle storage unitof the sample collection apparatus of FIGS. 1 and 2;

FIG. 4 is an exploded cross sectional view of the piston assembly andresin/sample collection apparatus of apparatus which fits into thesample collection apparatus of FIG. 1;

FIG. 5 is an enlarged cross sectional view of the resin/sample containerof FIG. 4;

FIG. 6 is an exploded view of the resin/sample container of FIG. 5;

FIG. 7 is a cross sectional view of a sample filtration purificationshuttle apparatus with direction of movement of the plunger shown byarrow D' and direction of flow of the fluid shown by arrows A;

FIG. 8 is a cross sectional view of the filtration purification shuttleapparatus of FIG. 7 with plunger depressed and sample ready for removal;

FIG. 9 is a cross sectional view of a filtration purification shuttlewith the shuttle storage unit and resin/sample container in a positionto be attached;

FIG. 10 is a cross sectional view of a filtration purification shuttleconnected to a resin/sample container with direction of movement of theplunger shown by arrow U and direction of flow of washing/elutingsolution through the resin/sample container shown by arrows B;

FIG. 11 is an alternate embodiment of the invention showing a removabledipstick unit;

FIG. 12 is a cross sectional view of the bottom surface of the dipstickunit shown in FIG. 11;

FIG. 13 is a cross sectional view showing movement of the dipstick unitsnug fitted into an alternate plunger with direction of movement of theplunger shown by arrow D and direction of flow of eluding concentratethrough the resin/sample container shown by arrows C;

FIG. 14 is a cross sectional view of the apparatus of FIG. 13 showingthe dipstick and associated testing strips reacting with concentratedand partially purified antigen;

FIG. 15 is an alternate embodiment of the invention showing a samplefiltration purification shuttle apparatus with the alternate shuttlestorage unit of the sample collection apparatus equipped with a needleand the air release opening closed with direction of movement of theplunger shown by arrow U, and direction of flow of the fluid shown byarrow A; and

FIG. 16 is a cross sectional view of a sample filtration purificationshuttle apparatus of FIG. 15 with the needle replaced with a stopper andthe air release plug removed with direction of movement of the plungershown by arrow D, and direction of flow of the fluid shown by arrows A.

DETAILED DESCRIPTION OF THE INVENTION

The preferred embodiment and best mode of the invention is seen in FIGS.1 and 3 through 8. The invention shown therein comprises a modular fluidresin/sample containment and sample preparation testing device. Whilethe invention can be used for any body fluid such as sputum, blood, bodyfluids or urine, it is primarily designed for use in collectingurine/blood samples for use in testing for the presence of various kindsof cancer in the body.

As shown in FIGS. 1 and 3, a sample collection apparatus 20 isconstructed of polystyrene and comprises a tubular collection unit 22, ashuttle storage unit 30 and an associated cap member 40. The tubularcollection unit 22 is constructed with a tubular open ended cylindricalbody 24 having formed on one end an open flared end portion 26 and onthe other end threaded portion 28. The flared end portion 26 has a widemouth to more easily receive body fluid which is loaded into the unitand also prevents entrapment of air between the resin container unit andthe surface of the sample fluid. The shuttle storage unit 30 isremovably secured to the threaded portion 28. The shuttle storage unit30 comprises a cylindrical cup shaped body 32 with a stepped femalethreaded open end 34 and shoulder 35. The open end 34 has a greaterdiameter than the diameter of body 32. A stop member 36 comprised of acircular ring or integrally formed rib is formed or secured to the innersurface of the shuttle body 32 immediately below the shoulder 35 of thethreaded stepped open end 34. This stop member 36 serves as a stop for atransporter or shuttle assembly 50 shown in FIG. 4 which will bediscussed later on in the specification. The alternate shuttle storageunit 130 shown in FIG. 2 is like shuttle storage unit 30 except for theneedle fitting opening at the bottom of the unit. It is intended for theuse of withdrawing blood or other body fluid samples directly from thepatient as will be discussed later on in the specification. The capmember 40 as shown in FIG. 3 is formed with a cylindrical body 42 havinga lid or cover 44 and external threads 46 which mate with the femalethreaded end portion 34 of the shuttle body 32. Thus the shuttle storageunit 30 and cap 40 can be used to form a closed container holding theparticulants testing material or fluid as desired. It should also benoted that a threaded or snug fitting cap (not shown) can be placed overend position 26 so that the sample collection apparatus can be closed.

The transporter assembly 50 as shown in FIG. 4 is designed to fit withincylindrical body 24 and slideably move along the interior wall surface25 in a sealed relationship and hold a shuttle resin/sample container 70for removal or deposit within the shuttle storage body 32. Thetransporter assembly 50 is constructed of a transparent plasticcomprising a hollow cylindrical piston body 52 provided with a thumbcover 54 and a bottom end member 55. An air release aperture 56 isformed in the piston body so that there is communication between theinterior chamber 53 of the piston body into the outside atmosphere. Amale threaded nipple 60 is formed on the outside of the bottom endmember 55 and is provided with a throughgoing aperture (not shown) whichcommunicates with the interior chamber 53. Mounted around the pistonbody in annular channels 61 and 63 cut into the exterior surface of thebody 52 are respectively an upper O-ring 62 and lower O-ring 64. TheseO-rings slideably engage and form a fluid seal against the interiorsurface 25 of sample collection unit 22. A shuttle resin/samplecontainer 70 is adapted to be mounted to the nipple 60 and has adiameter or size sufficient to allow it to be seated within the interior33 of shuttle storage unit 30.

The shuttle sample container 70 as clearly shown in FIGS. 5 and 6 isconstructed with a cylindrical body 80 open at both ends and threaded onthe outside to allow the mounting of a circular top cover 74 which isthreaded on the inside of the cylindrical skirt 72 and provided athroughgoing threaded aperture 76. If desired to improve fluid flow, thetop cover 74 can be provided with a plurality of apertures (not shown)which enhance flow through the cover into piston chamber 53. It is ofcourse apparent that the piston bottom end member 55 would also beconstructed with complimentary throughgoing apertures. The throughgoingaperture 76 is adapted to receive and mate with the threaded male nipple60 to allow the same to be fastened to transporter assembly 50 orselectively removed from the transporter assembly 50. A circular bottomcover 78 with a plurality of throughgoing apertures 79 threaded on theinside of its cylindrical skirt 71 is threaded onto the other end ofbody 80. Positioned inside the body 80 is a snug fitted cylindricalresin module 90. The resin module 90 comprises a cylindrical body 92 andend walls 94 and 96. Both end walls 94 and 96 are formed with porousseptums 98 to allow easy flow through of the fluids. A filtrationmembrane 100 preferably between 0.2-0.5 microns in thickness ispositioned between the bottom cover 78, a seal ring 101, and the lowerporous end wall 96.

If desired a plurality of membranes can be stacked to obtain the desiredfiltration. An O-ring sleeve 102 comprising a plurality of O-rings 104is mounted to the exterior surface of the cylinder formed by the skirtsides of both top and lower covers 71, 72 when the same are fullyscrewed onto the body of the resin module container 80. 103 of thesleeve 102 abut closely against the planar inner surfaces of the topcover 74 and bottom cover 78 as can be seen in FIG. 5. The resin module90 may be filled with resin/sample 200 consisting of beads of all formsand sizes which can be specifically manufactured for ion exchange (e.g.Mono Q anion exchange, and Mono P cation exchange from Pharmacia), highaffinity chromatography or hydrophobicity (e.g. phenylsepharose beads).Preferably the module holds high affinity resin with specific antibodiesimmobilized onto the solid phase resin (e.g. protein A, . . .etc.) sothat antigens in the sample can bind to their specific antibodies whilepassing through the resin module and become immobilized as well.

FIG. 7 shows the sample collection apparatus containing a urine sample300 having particulate matter 302 therein with a transporter assembly 50and associated resin/sample container 70 mounted therein. As the shuttleresin/sample container 70 and its associated O-rings 104 is mounted inthe interior of the sample collection unit 22, adjacent surface 25,piston 52 is pushed down in the direction shown by arrow D causing thefluid sample 300 to pass through the bottom wall 78, membrane 100 whichfilters the particulate matter 302, resin module 90 and threadedaperture 76 into the chamber 53. It should be noted that the aircontained in chamber 53 is pushed out by the fluid through air releaseaperture 56 into a chamber formed by the concentric outer surface of thepiston body 52 and the inner surface 25 of sample collection unit 22.The shuttle resin/sample container 70 is pushed down until it entersinto the body cavity 33 at which time the lower O-ring 64 engages stoprib 36 thus seating the shuttle resin/sample container 70 in apredetermined position so that it cannot break or damage the shuttlestorage unit 30. When the shuttle resin/sample container 70 is seated inthe shuttle storage unit 30, the upper "O" ring 62 becomes engaged withthe inner surface 25 of cylindrical body 24. This will discontinue thecommunication between the body cavity 53 and the atmosphere through theair release aperture 56. Consequently the fluid entering the body cavity53 will be trapped inside it even after removal of the shuttle storageunit 30 together with the seated resin/sample container 70. It will alsobe noted that the particulate matter which has been screened byfilteration membrane 100 is thus concentrated at 304 in the bottom ofchamber 33 as shown in FIG. 8.

The resin sample material 200 having had flow contact with the fluid 300captures the specific component of the fluid which is to be tested; inthis example, antigens caused by cancer cells. The shuttle storage unit30 is then unscrewed from the tubular collection unit 22 with theshuttle resin/sample container 70 contained therein, the transporterassembly 50 remaining with the tubular collection unit 22 and cap 40 isscrewed on threaded end 34 to keep the sample in a secured containedcondition for analysis of the particulate matter or other materialscaptured by the beads in the resin/sample container.

If desired the sample or material trapped in the resin/sample container70 can be washed prior to or after transporting it to the area desiredfor testing. This washing is shown in FIGS. 9 and 10 in which aprepacked washing/preservative solution module 110 filled with aprepackaged washing and/or preservative solution 112 (e.g. Phosphatebuffer saline, tris Hcl buffer, . . . with or without sodium azide as abacteriostatic agent) is screwed into the aperture 76 of the impregnatedresin/sample container 70 by means of a threaded nipple as previouslydisclosed and placed in a collection apparatus 20 filled with washingsolution. The construction of the prepacked washing solution module 100combines that of the transporter assembly 50 mounted in samplecollection apparatus 20. The plunger of the piston is pulled upward inthe direction of arrow U as shown in FIG. 10 so that washing solution112 flows downward through the resin/sample container 70 into chamber 33of the shuttle storage unit 30. Washing the resin/sample container 70with the washing buffer solution 112 provides a washed sample.

In an alternate embodiment of the invention as shown in FIG. 11 anangular dipstick or testing strip member 120 is provided with aplurality of angular flat sides 122 each of which holds a testing strip124. The dipstick member 120 is mounted in a testing module 150 which isidentical to that previously discussed differing only in that the bodyfluid as shown in FIG. 7 has been replaced with an elution buffersolution 140 and the dipstick member 120 is to fit tightly positioned inchamber 53 of the piston body. The top cover 154 of the piston can alsobe provided with an aperture 156 receives a screw cap 158 (not shown) toseat and hold the testing strip member 120 in place. FIG. 12 is a crosssectional view showing the bottom surface of the angular dipstick module120. A central groove 125 connected to engraved channels 126, directsand distributes the fluid to the dipstick housing. The central groovefits into the nipple hole of the nipple in the dipstick transporterassembly 150. The testing strip member is shown in FIG. 11 and while itis octagonal, it is recognized that it can have any number of sides tohold any number of testing strips to get a plurality of differentresults such as for example; test strips to test for cancer associatedantigens such as transforming growth factors (TGFs), tumor cell motilitystimulation factor(s) (AMF), tumor specific markers (e.g. specificprostate cancer marker, aplpha fetoproteins..etc), and test strips totest for proteolytic enzymes associated with tumor invasion andmetastases (e.g. collagenases, cathepsins, proteases, . . . etc).

In this strip testing procedure the test resin/sample container 170 isscrewed into the end of the dipstick transporter assembly 150 in thesame manner as previously disclosed and is slid into an eluding bufferunit 160. The removable dipstick unit 120 and associated piston ispushed downward as indicated by arrow D into the eluding buffer solutionso that the multiple test strips 124 are soaked with concentrated andpartially purified antigen as shown in FIG. 14. The total unit can thenbe shipped for testing or held for testing the dipsticks or individualtesting strips.

In FIG. 15 an alternate embodiment of the shuttle storage unit is shownwhere the body of shuttle storage unit 32 is replaced with the alternatebody 180 with lure lock opening at the bottom as previously shown inFIG. 2. This permits the use of the device to act as a syringe towithdraw and process blood samples from patients at the same time. Asshown in FIG. 15 the air release aperture 56 is blocked with a removableplug 181 during the process of withdrawing blood from the patient and aneedle 183 is shown in a locked in position 182. After withdrawing theblood sample the needle is replaced with a lure lock 186 as shown inFIG. 16. The air release plug 181 is then removed and the blood sample184 and 185 (fluid and particulate matter) will be processed asdescribed earlier in the text.

It can thus be seen that the present invention provides a unique modularusage for collecting, filtering, concentrating, transporting, andpurifying the biological fluid sample for use in testing for disease orother analysis.

In the foregoing description, the invention has been described withreference to a particular preferred embodiment, although it is to beunderstood that specific details shown are merely illustrative, and theinvention may be carried out in other ways without departing from thetrue spirit and scope of the following claims

What is claimed is:
 1. An apparatus for collecting biological fluids andholding a predetermined sample for testing comprising a tubularcontainer having open ends; a collection storage unit removably securedto one of said container ends, said collection storage unit having anopen end and a closed end, a shuttle assembly slidably mounted in saidtubular container, said shuttle assembly comprising a cylindrical hollowpiston defining a chamber, a testing means mounted in said pistonchamber, a top cover covering one end of said piston and fluid flowmeans formed on the other end of said piston, said fluid flow meanscomprising an end member with a connector means mounted therein, saidconnector means defining a throughgoing bore communicating with saidpiston chamber, "O" ring means mounted on the exterior surface of saidpiston to form a fluid tight seal between said "O" ring means and theinterior surface of said elongated tubular container, and samplecontainer means removably secured to said connector means and adapted tobe seated in said collection storage unit.
 2. An apparatus as claimed inclaim 1 wherein said testing means comprises a testing body and aplurality of testing strips mounted to said testing body.
 3. Anapparatus for collecting biological fluids comprising a tubularcontainer having open ends; a collection storage unit removably securedto one end of said container, said collection storage unit having anopen end and a closed end, a shuttle assembly slidably mounted in saidtubular container, said shuttle assembly comprising a cylindrical hollowpiston defining a chamber, testing means mounted in said chamber, saidtesting means comprising a body and testing strip means mounted to saidbody, a top cover covering one end of said piston and fluid flow meansmounted on the other end of said piston, said fluid flow meanscomprising an end member with connector means mounted therein, saidconnector means defining a throughgoing bore communicating with saidpiston chamber, "O" ring means mounted on the exterior surface of saidpiston cylinder to form a fluid tight seal between said "O" ring meansand the interior surface of said elongated tubular container, and samplecontainer means removably secured to said connector means.
 4. Anapparatus as claimed in claim 3 wherein said testing strip meanscomprises test strips to test for cancer associated antigens such astransforming growth factors.
 5. An apparatus as claimed in claim 3wherein said testing strip means comprises test strips to test for tumorcell mobility stimulation factors.
 6. An apparatus as claimed in claim 3wherein said testing strip means comprises test strips to test for tumorspecific markers.
 7. An apparatus as claimed in claim 6 wherein saidtumor specific marker is alpha fetoproteins.
 8. An apparatus as claimedin claim 3 wherein said testing strip means comprises test strips totest for proteolytic enzymes associated with tumor invasion andmetastatses.
 9. An apparatus as claimed in claim 8 wherein saidproteolytic enzyme is collagenases.
 10. An apparatus as claimed in claim8 wherein said proteolytic enzyme is cathepsins.
 11. An apparatus asclaimed in claim 8 wherein said proteolytic enzyme is proteases.
 12. Anapparatus as claimed om claim 3 wherein said testing strip meanscomprises a plurality of testing strips, each testing strip indicating aresult when contacted by fluid passing through said sample container.